Microencapsulation is the method of choice for developing parenteral formulations for long-term drug delivery. However, current methods of microencapsulation present a number of difficulties in microencapsulation of protein drugs. For this reason, only a limited number of successes have been reported using the conventional methods. The objective of this project is to develop a new microencapsulation system utilizing well-established flow cytometry technology to produce homogeneous polymeric microcapsules that can control the drug release rate while maintaining the stability of the encapsulated drug throughout the lifetime of the product. In this new technique, which we call the Microenvironment-Controlled Encapsulation (MICE) process, highly homogeneous mononuclear microcapsules are generated by hydrodynamically focusing the component liquids using a flow cytometer. This project is based on the hypotheses that (a) the mechanical and chemical stresses on the encapsulated drugs can be minimized by separately processing the component materials; and (b) homogeneous microcapsules can be obtained by precise control of specific environments in which the microcapsules form. The specific aims of this project are: (1) to understand and optimize the MICE process; (2) to gain control over the microenvironment; (3) to characterize the physical properties of the microcapsules and the integrity of encapsulated protein; and (4) to provide a microcapsule system that is capable of controlling the in vitro drug release rate. The significance of the MICE process is that microcapsules, which are highly homogeneous in size and geometry, can be produced at a high frequency by taking advantage of existing flow cytometry technology with minimal stresses to the encapsulated drugs. The MICE process will facilitate microencapsulation of a variety of protein drugs that have been difficult to formulate with the conventional methods, as well as small molecular weight drugs.